TL1A is a TNF-superfamily member produced by endothelial cells, dendritic cells, monocytes and other immune cells. TL1A signals through DR3-a TNF receptor-superfamily member expressed by activated T-cells and other immune cells. Receptor ligation by TL1A leads to increased proliferation and cytokine production by T-helper effector cells. DR3 and TL1A are involved in RA and CD and antagonizing the DR3-induced effects would therefore be desirable in treatment of inflammatory diseases such as e.g. RA (Rheumatoid Arthritis) and CD (Crohns Disease).
WO2011106707 discloses a DR3 specific antibody (11H08), as well as variants thereof, comprising the 11H08 CDR sequences (SEQ ID NO 14+15) inserted into various antibody frameworks. The 11H08 antibody binds DR3 with a relatively low affinity and it does not bind to the CRD1 domain. There is thus a need in the art for DR3 antagonists useful for treating inflammatory diseases.